374 Colchicine 



of importance for quantitative work, the changes that colchicine may 

 undergo in solution are far more important, especially for work with 

 warm-blooded animals or tissue cultures. Colchicine solutions should 

 always be freshly prepared, or kept protected from the action of 

 oxygen and light. For work on plants, where rather concentrated 

 solutions are used and where no problems of general toxicity arise, 

 this is not so important. In animal work, and especially for all work 

 on birds or mammals, it is most important to use freshly prepared 

 solutions.43 Standing in the presence of air, colchicine appears to 

 undergo a slow oxidation about which little is known (cf. Chapter 7) . 

 This decreases the spindle-inhibiting action, but may not affect simi- 

 larly the general toxicity, which is increased in cold-blooded animals 

 such as frogs.-^^ These remarks apply to solutions, whether in water 

 or fatty solvents. The latter have been mainly used for local applica- 

 tions in cancer chemotherapeutic tests. i*^- '^ 



The important point is that each paper should mention clearlv 

 the origin of the colchicine, whether crystalline or not, whether puri- 

 fied and how, the method of preparing the solutions before the ex- 

 periments, and the temperature at which these are conducted. It is 

 only in this way that a valid comparison of results is possible. 



16A.2: Temperature 



In Chapter 7, several instances have been given of the effect of 

 temperature on the action of colchicine. This has long been known, 

 but has often been overlooked.^^^ Most workers mention that the 

 alkaloid docs not influence cell division in unicellular organisms 

 (cf. Chapter 4) . However, while Paramecium is unaffected by colchi- 

 cine solutions at a one per cent concentration at 15°C., the same 

 solutions kill the paramecia in less than 4 hours at 33°C. Exposure 

 to this temperature is in itself not harmful to the organisms.^-^ 



These temperature effects are not yet understood properly. They 

 explain the considerable differences between colchicine pharmacology 

 in cold-blooded animals and in birds and mammals (cf. Chapter 7) . 

 For instance, colchicine-arrested metaphases remain intact for hours 

 and even days (Fig. 2.2) in amphibia; in mammals, on the contrary, 

 the nucleus of a cell arrested at metaphase by a spindle poison under- 

 goes rapid destruction. In all in vitro ^\ork, the temperature should 

 be constant and checked carefully. 



16A.3: The Study of Mitosis 



Colchicine may be utilized for many different purposes when 

 analyzing mitotic growth, and techniques may considerably differ. 

 For instance, in studies on the morphology of chromosomes or pseudo- 

 spindle in arrested metaphases, quantitative data, except those about 



